FORMULATIONS OF BENDAMUSTINE
Long term storage stable bendamustine-containing compositions are disclosed. The compositions can include bendamustine or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable fluid which can include in some embodiments PEG, PG or mixtures thereof and an antioxidant or chloride ion source. The bendamustine-containing compositions have less than about 5% total impurities, on a normalized peak area response (“PAR”) basis as determined by high performance liquid chromatography (“HPLC”) at a wavelength of 223 nm, after at least about 15 months of storage at a temperature of from about 5° C. to about 25° C.
1 . A solution comprising:
100 mg of bendamustine, or a pharmaceutically acceptable salt thereof, wherein the concentration of the bendamustine in the solution is 25 mg/ml; and
5 mg/ml of monothioglycerol,
wherein the bendamustine, or pharmaceutically acceptable salt thereof, and the monothioglycerol are dissolved in a pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol and glycofurol;
wherein the total impurities resulting from the degradation of the bendamustine is less than about 5% peak area response, as determined by HPLC at a wavelength of 223 nm after at least about 15 months at a temperature of about 5° C. to about 25° C.
2 . The solution of claim 1 , wherein the solution is stable for at least about 15 months at 5° C. or for at least about 15 months at 25° C.
3 . The solution of claim 1 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and one or more of propylene glycol, ethanol, benzyl alcohol, and glycofurol.
4 . The solution of claim 1 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol.
5 . The solution of claim 1 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and propylene glycol.
6 . The solution of claim 1 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and ethanol.
7 . The solution of claim 1 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and benzyl alcohol.
8 . The solution of claim 1 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and glycofurol.
9 . The solution of claim 1 , wherein the solution comprises about 100 mg of bendamustine, or a pharmaceutically acceptable salt thereof.
10 . The solution of claim 1 , wherein the solution comprises about 100 mg of bendamustine.
11 . A sterile vial containing the solution of claim 1 .
12 . The sterile vial of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and one or more of propylene glycol, ethanol, benzyl alcohol, and glycofurol.
13 . The sterile vial of claim 11 , wherein the bendamustine concentration in the composition is 25 mg/mL.
14 . The sterile vial of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol.
15 . The sterile vial of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and propylene glycol.
16 . The sterile vial of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and ethanol.
17 . The sterile vial of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and benzyl alcohol.
18 . The sterile vial of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and glycofurol.
19 . A method of treating leukemia in a human in need thereof comprising providing a solution according to claim 1 , diluting the solution, and intravenously administering the diluted solution to the human.